The goal of the research is to further our understanding of the biochemical mechanisms underlying hormonal regulation of reproductive (estrous) behavior. This application focuses on the relationships between the biochemical and behavioral actions of estradiol (E2), an ovarian steroid that plays a pivotal role in the induction of female reproductive behavior. Since the hypothalamus (HYP) and preoptic area (POA) of the diencephalon have been identified as brain sites at which E2 acts to bring about estrous behavior, the proposed experiments investigate E2 action in the HYP-POA. This laboratory and others have provided correlative evidence that the interaction of E2 with high affinity binding proteins (receptors) in the HYP-POA is a prerequisite for the hormonal activation of female sexual behavior. The proposed research will begin to fill in the gaps in our knowledge of how E2 binding to receptors in neurons of the HYP-POA ultimately results in the expression of estrous behaviors many hours later. To accomplish this objective, the proposed studies will evaluate whether E2-induced conformational changes in the receptor protein and the subsequent binding of the hormone-receptor complex to chromatin material within HYP-POA cell nuclei are correlated with the induction of female reproductive behavior. Biochemical studies will define more precisely the molecular interactions between E2-receptor complexes and HYP-POA chromatin and will assess the role of these interactions in hormonal activation of estrous behavior. Additional experiments will examine E2 regulation of noradrenergic neurotransmission in vivo and in vitro to test the hypothesis that estrogen facilitation of noradrenergic activity in the HYP is involved in hormonal activation of reproductive behavior.